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Verfasst von:Samra, Vanessa [VerfasserIn]   i
 Flach, Johanna [VerfasserIn]   i
 Naumann, Nicole [VerfasserIn]   i
 Brendel, Susanne [VerfasserIn]   i
 Kleiner, Helga [VerfasserIn]   i
 Weiß, Christel [VerfasserIn]   i
 Seifarth, Wolfgang [VerfasserIn]   i
 Nowak, Daniel [VerfasserIn]   i
 Hofmann, Wolf-Karsten [VerfasserIn]   i
 Fabarius, Alice [VerfasserIn]   i
 Popp, Henning [VerfasserIn]   i
Titel:Antileukemic efficacy in vitro of talazoparib and APE1 inhibitor III combined with decitabine in myeloid malignancies
Verf.angabe:Vanessa Kohl, Johanna Flach, Nicole Naumann, Susanne Brendel, Helga Kleiner, Christel Weiss, Wolfgang Seifarth, Daniel Nowak, Wolf-Karsten Hofmann, Alice Fabarius and Henning D. Popp
E-Jahr:2019
Jahr:3 October 2019
Umfang:16 S.
Fussnoten:Gesehen am 06.12.2019
Titel Quelle:Enthalten in: Cancers
Ort Quelle:Basel : MDPI, 2009
Jahr Quelle:2019
Band/Heft Quelle:11(2019,10) Artikel-Nummer 1493, 16 Seiten
ISSN Quelle:2072-6694
Abstract:Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials.
DOI:doi:10.3390/cancers11101493
URL:kostenfrei: Volltext: https://doi.org/10.3390/cancers11101493
 kostenfrei: Volltext: https://www.mdpi.com/2072-6694/11/10/1493
 DOI: https://doi.org/10.3390/cancers11101493
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:acute myeloid leukemia
 APE1 inhibitor III
 apurinic/apyrimidinic endonuclease 1
 chronic myelomonocytic leukemia
 myelodysplastic syndrome
 poly(ADP ribose) polymerase 1/2
 talazoparib
K10plus-PPN:1684691494
Verknüpfungen:→ Zeitschrift
 
 
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